Resumo

Objectives: Considering that the methylphenidate (MPH) is one of the most frequently prescribed psychostimulants for attention-deficit hyperactivity disorder, yet the long-term neurochemical consequences of treatment are unknown, in the present study we investigated the effects of chronic administration of MPH to juvenile rats on spatial memory, brain-derived neurotrophic factor immunocontent and acetylcholinesterase activity in hippocampus and prefrontal cortex. Methods and Results: For the chronic treatment, male Wistar rats received intraperitoneal injections of MPH (2.0 mg/Kg) once a day, from the 15th to the 45th day of age or an equivalent volume of 0.9% saline solution (controls). Twenty-four hours after the last injection, animals were subjected to testing in the Morris water maze. After that, animals were killed and hippocampus and prefrontal cortex were obtained for determination of brain-derived neurotrophic factor immunocontent and acetylcholinesterase activity. Results showed that chronic administration of MPH affects the acquisition phase of reference memory in days 2 (control: 34.47&#+1773.53; MPH: 48.16&#+1773.55; n=12) and 4 (control: 24.02&#+1772.61; MPH: 37.31&#+1774.61; n=12). In the test session, the latency to cross over the platform location for the first time was significantly increased by MPH treatment when compared to saline group (control: 10.41&#+1771.26; MPH: 25.91&#+1775.34; n=12). We also showed that chronic MPH administration affects performance of rats on trials 3 (control: 17.98&#+1772.56; MPH: 32.46&#+1773.60; n=12) and 4 (control: 11.0&#+1771.05; MPH: 27.28&#+1771.64; n=12) of working memory. In order to verify whether MPH would affect motor activity, we submitted both groups to the open field arena. MPH did not alter the number of crossings when compared to saline group (control: 30.66&#+1772.62; MPH: 33.23&#+1774.29; n=12). In addition, our results showed that treatment with MPH did not affect brain-derived neurotrophic factor immunocontent (control: 9.87&#+1770.82; MPH: 9.75&#+1771.45; n=5) nor acetylcholinesterase activity (control: 1.33&#+1770.88; MPH: 1.50&#+1770.28; n=6) in hippocampus. However, its administration significantly reduced brain-derived neurotrophic factor levels (control: 5.60&#+1770.56; MPH: 4.54&#+1770.64; n=5) and increased acetylcholinesterase activity (control: 1.44&#+1770.76; MPH: 2.24&#+1770.45; n=6) in prefrontal cortex of experimental animals. Results are expressed as mean ± SEM. Conclusions: Our results suggested that the deficit in spatial memory may be related to decreased brain-derived neurotrophic factor immunocontent and increased acetylcholinesterase in prefrontal cortex of young rats subjected to MPH administration. These results, together, showed that the MPH causes neurochemical and behavioral changes in animals, which can be harmful to brain development. Financial support: PROPESQ/UFRGS, CNPq.